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Biomedical subjects

Y Kariya

Publications and source records attributed to Y Kariya.

At least 19 recordsLinked to original sources

Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2.

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16+ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN) alpha, IFN gamma, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (alpha chain) or p75 (beta chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

Adenocarcinoma

Preparation of unsaturated disaccharides by eliminative cleavage of heparin and heparan sulfate with heparitinases.

1. Six kinds of unsaturated disaccharides were prepared by enzymatic digestion of heparin and heparan sulfate with heparitinases I0 and IV, and subsequent column chromatography. They were identified by HPLC showing good separation from each other. 2. The content of each unsaturated disaccharide fraction was determined colorimetrically, and found to range from 130.7 to 722.3 mumol. 3. Molecular extinction coefficient of each unsaturated disaccharide was calculated from absorbance at a wavelength of around 230 nm where a peak appeared on the ultraviolet spectrum of each disaccharide solution at pH 2. The values varied from 6000 to 6600.

Animals

Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK.

The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems.

Adult

Suppression by human placental protein 14 of natural killer cell activity.

Human decidua of early pregnancy contains considerable numbers of CD3-CD56+ natural killer (NK) cells. In this study, two major protein products of the decidua, placental protein 14 (PP14) and placental protein 12 (PP12), were tested for the ability to regulate human NK cell activity. In vitro overnight exposure to PP14 of blood lymphocytes or purified large granular lymphocytes (LGL) resulted in suppression of cytotoxicity against K562 target cells in a 4-h 51Cr release assay. The NK inhibition was dependent on concentrations of PP14, being detectable at 5 micrograms/ml and reaching maximum at 50 micrograms/ml. Manifestation of PP14-induced NK suppression required 18-h contact with NK cells. The suppression of NK activity by PP14 was not abolished by indomethacin. In a target binding assay the number of PP14-treated LGL binding to K562 was comparable to that of untreated ones. By contrast with PP14, PP12 produced no effects on NK cells. These results indicate that PP14 suppresses the function of NK cells, which might be involved in prevention of maternal immune rejection of fetus at the fetomaternal interface.

Cells, Cultured

Interleukin-1 inhibits in vitro decidualization of human endometrial stromal cells.

Interleukin-1 (IL-1), a critical cytokine for the initiation of the immune response to infection or antigenic challenge, is known to also possess a variety of biological functions outside the immune system. We examined whether IL-1 could affect the decidualization of human endometrial stromal cells (ESC), a conspicuous part in the process of implantation, by assessing PRL production and morphological transformation in an in vitro system. Purified human ESC were cultured in the presence of progesterone (P) with or without the addition of IL-1. IL-1 markedly suppressed the induction of PRL production by P in a dose-dependent manner. The morphological decidualization of ESC in response to P was also inhibited by IL-1. This report demonstrates for the first time the possibility that IL-1 blocks decidualization, the functional differentiation of human endometrial stromal cells in response to ovarian steroids.

Cell Count

Prediction of postoperative clinical course by autologous tumor-killing activity in lung cancer patients.

Fifty patients with primary localized lung cancer were tested at the time of surgery for the ability of their lymphocytes to kill autologous, freshly isolated tumor cells, and the assay was evaluated for prognostic significance. Peripheral blood lymphocytes of 27 patients (54%) demonstrated significant autologous tumor-killing activity in 6-hour 51Cr-release assays. Twenty-three of the 27 patients with autologous tumor-killing activity remained tumor free and survived more than 5 years after curative surgery, while all 23 who were negative for autologous tumor-killing activity relapsed by 18 months after surgery and died within 42 months after surgery. The differences in survival curves for the two groups were highly significant (P less than .00003). Autologous tumor-killing activity was not correlated with natural killer (NK) cell activity against K562 human myeloid leukemia cells or proliferation of lymphocytes stimulated with autologous, freshly isolated tumor cells in mixed culture. There were no differences in total survival between patients with positive results and those with negative results in tests of NK cell activity and autologous mixed lymphocyte-tumor culture reaction. These results indicate that autologous tumor-killing activity is a meaningful prognostic indicator and provide evidence for immunological control of tumor growth and metastasis. According to our preliminary data, it is unlikely that lung cancer patients who remain tumor free after 60 months of follow-up will develop recurrence or die from the disease. We are conducting a study to determine whether induction of autologous tumor-killing activity before surgery, by treatment with biological response modifiers,can improve the clinical outcome in patients who do not naturally have this potential.

Adult

Occurrence of chondroitin sulfate E in glycosaminoglycan isolated from the body wall of sea cucumber Stichopus japonicus.

Glycosaminoglycan was isolated from the body wall of sea cucumber Stichopus japonicus by a method consisting of enzymatic digestion, gel filtration, and ion-exchange chromatography. One gram of sea cucumber glycosaminoglycan was composed of 2.50 mmol of sulfate, 0.47 mmol of N-acetylgalactosamine (GalNAc), 0.53 mmol of glucuronic acid (GlcA), 1.73 mmol of fucose, and a small amount of peptide. When mildly hydrolyzed with 0.1 N H2SO4, this glycosaminoglycan released two products, one consisting of fucose plus sulfate and the other of fucose only. Partially hydrolyzed glycosaminoglycan thus obtained was composed of sulfate, GalNAc, GlcA, and fucose at a molar ratio of 3:2:2:1. Partially hydrolyzed glycosaminoglycan was easily digested with chondroitinase AC II. In ion-exchange chromatography, the digest exhibited four sharp peaks whose retention times agreed with those of unsaturated 0-(delta Di-0S), mono-(delta Di-4S and delta Di-6S), and di-(delta Di-SE) sulfated disaccharide, respectively. The disaccharide unit of sea cucumber glycosaminoglycan was composed of 22.4% chondroitin sulfate E, 11.2% chondroitin, 10.4% chondroitin 4-sulfate, and 56.0% chondroitin 6-sulfate.

Animals

Studies on T-lineage cells in human decidua of first trimester pregnancies.

T-lineage cells in human decidua of early pregnancies were tested for surface markers, proliferative response, interleukin-2 (IL-2) production, and natural killer (NK) activity. T-lineage (CD2+) cells that were obtained from decidua by the use of E-rosette formation contained fewer CD3+ mature T cells and CD4+ cells than those from the peripheral blood of the same donors, while no differences were seen in the frequencies of CD8+ cells. P55 molecules of IL-2 receptor (IL-2R/p55, Tac antigen) were hardly detected on fresh decidual T-lineage cells, though approximately 20% were positive for HLA-DR. More than a half of decidual T-lineage cells expressed CD56 molecules on their surface and killed K562 cells, the prototype target of NK cells, while most of them were negative for CD16 and CD57. Upon stimulation with IL-2, decidual T-lineage cells demonstrated dose-dependent proliferative response. In addition, they were induced to produce high amounts of IL-2 by stimulation with mitogens but not with alloantigens. These results suggest that human decidua contains high numbers of CD2+3-CD16 +/- 56+ lymphocytes and that this population responds to IL-2, produces IL-2 and mediates NK activity.

Decidua

Glycosaminoglycan involved in the cation-induced change of body wall structure of sea cucumber Stichopus japonicus.

The body wall of sea cucumber Stichopus japonicus was treated with various concentrations of several cations, and examined for changes in toughness, taking punch force as parameter. Toughness of the body wall tended to decrease with increasing concentration of each cation, but in different modes depending mainly upon the valency of cation: e.g., the body wall completely lost toughness in 0.3 M Na+ or 0.4 M K+, whereas it retained more than half the initial toughness even in 0.4 M Ca2+ or Mg2+. Glycosaminoglycan (GAG) from the body wall was dissolved in water, and examined for viscosity changes as caused by those cations. Specific viscosity (eta sp) decreased from 0.71 (without cation) to 0.47-0.57 in the presence of 0.1 M monovalent and divalent cations. At 0.4 M, monovalent cations reduced eta sp to 0.38-0.46, but divalent cations increased eta sp to 0.56-0.63. Electron microscopy demonstrated that GAG matrix was clearly observed in the absence of cation, but disappeared in 0.4 M NaCl, forming wide free spaces in the body wall. These results all suggested that GAG is closely involved in the change of toughness of sea cucumber body wall.

Animals

[In vitro combined effects of pirarubicin (THP) and various antitumor drugs on human tumor cell lines].

The combined effects of pirarubicin (THP) and various antitumor drugs on HeLa S3 human uterine cervix carcinoma and K562 human myelocytic leukemia cells were determined by enhancement of their cytotoxic activities. The combination of 0.15 microgram/ml THP with cisplatin (CDDP), mitomycin C (MMC), peplomycin (PEP), 5-fluorouracil (5-FU), methotrexate (MTX), enocitabine (BH-AC) or etoposide showed synergistic effects on HeLa S3 cells. Also, the combination of 0.01 microgram/ml THP with CDDP, BH-AC or etoposide showed synergistic effects on K562 cells. Especially, the combined effects of THP with MMC or MTX were remarkable, and the combination under almost all concentrations of MMC or MTX showed synergistic effects on HeLa S3 cells. On the other hand, the combination of adriamycin (ADM) with MMC or MTX did not show such a remarkable effects on HeLa S3 cells.

Antineoplastic Combined Chemotherapy Protocols

Arthroscopically aided anterior cruciate ligament reconstruction using a new drill wire guide.

The authors have made a new drill wire guide of universal type used in arthroscopic operations and have named it the Rhomboid Guide because of its rhomboidal frame. This multipurpose guide has made it easy to prepare exact bone tunnels under arthroscopic control and is preferably applied to arthroscopically aided anterior cruciate ligament (ACL) reconstruction. For such reconstruction the authors make a bifurcate intraarticular substitute using the iliotibial band. The Rhomboid Guide has made it possible to perform this rather complicated procedure arthroscopically.

Arthroscopy

Magnetic resonance imaging and spectroscopy of thigh muscles in cruciate ligament insufficiency.

In 21 patients with injury-related, chronic, anterior cruciate ligament insufficiency, 1H-magnetic resonance (MR) imaging and 31P-MR spectroscopy of the quadriceps muscles were performed with a systemic superconductive MR apparatus. The quadriceps of the noninjured side was used as the control. The quadriceps had a reduced cross-sectional area, but the knee flexors were not reduced. T2 values were prolonged in the vastus lateralis, medialis, and intermedius, but those of the rectus femoris were not. Phosphocreatine per inorganic phosphate measured with 31P-MR spectroscopy was decreased in the atrophied muscles, which correlated with the muscular cross-section. There was no difference in the muscular pH as recorded by the chemical-shift measurements of phosphocreatine and inorganic phosphate. Serial measurements of muscle cross-sectional area and high-energy phosphate bonds reflect the recovery of muscles.

Adenosine Triphosphate

Antitumor activity of pyrindamycins A and B.

Pyrindamycins A(1) and B(2) exhibited stronger cytotoxic activities than doxorubicin towards murine and human tumor cell lines and especially towards doxorubicin-resistant cells. Pyrindamycins A and B were also active in vivo against P388/ADR, a multidrug-resistant tumor cell line. Intracellular accumulation of pyrindamycins A and B in P388/ADR was the same as in P388. These antibiotics strongly inhibited DNA synthesis compared with RNA or protein synthesis. They showed significant therapeutic effects towards murine leukemia, but not to solid tumors.

Animals

Molecular cloning and nucleotide sequence of tuna growth hormone cDNA.

cDNA for mRNA of tuna growth hormone (GH) was cloned by screening a cDNA library constructed from tuna pituitary gland poly(A)+ RNA. The nucleotide sequence of cDNA (911 bases) revealed an open reading frame of 615 nucleotides, including a sequence (51 bases) for a possible secretory protein leader peptide. Noncoding regions were found in the nucleotide sequences up- (5'-terminal: 65 bases) and down- (3'-terminal: 231 bases) stream of the open reading frame. An amino-acid sequence deduced from the nucleotide sequence of the cDNA was identical with that determined in the purified tuna GH. Tuna GH was composed of 187 amino acids, and had a calculated molecular weight of 21,275. Amino-acid sequencing showed that there was one possible N-glycosylation site at Asn (Asn-Cys-Thr). Tuna GH showed amino-acid sequence homologies with chum salmon (67%), yellow tail (90%) and with human (32%) growth hormones.

Amino Acid Sequence